ArticleInternational journal of molecular sciences2022
Elevation of Anticancer Drug Toxicity by Caffeine in Spheroid Model of Human Lung Adenocarcinoma A549 Cells Mediated by Reduction in Claudin-2 and Nrf2 Expression.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Unlocking the Potential of Spheroids in Personalized Medicine: A Systematic Review of Seeding Methodologies.International journal of molecular sciences · 2025Pooled it
- Modulatory Effects of Cirsimarin on Lung Cancer A549 Cells Migration in 2D and 3D Cultures Involves Transcriptional Regulation of Metalloproteinases.Journal of biochemical and molecular toxicology · 2026Article
- Theobromine as a molecular switch: targeting Nrf2 pathway in invasive and non-invasive bladder cancer.Journal of natural medicines · 2026Article
- Caffeine May Delay the Radiation-Induced Nucleoshuttling of the ATM Kinase and Reduce the Recognition of the DNA Double-Strand Breaks in Human Cells.Biomolecules · 2025Article
- Association of dietary intake of theobromine with periodontitis: NHANES 2009-2014.BMC oral health · 2025Article
- Plant-Derived Anti-Cancer Therapeutics and Biopharmaceuticals.Bioengineering (Basel, Switzerland) · 2024Review
- Roles of Phytochemicals in Cancer Prevention and Therapeutics.International journal of molecular sciences · 2024Article
- Caffeine and neonatal acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2024Review
- Claudins in Cancer: A Current and Future Therapeutic Target.International journal of molecular sciences · 2024Review
- Deciphering the role of claudins in lung cancer.Frontiers in oncology · 2024Review
- Alkaloids as Natural NRF2 Inhibitors: Chemoprevention and Cytotoxic Action in Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Claudin-2 (CLDN2), a component of tight junctions, is abnormally expressed in human lung adenocarcinoma tissue. CLDN2 contributes to chemoresistance in human lung adenocarcinoma-derived A549 cells, and it may be a target for cancer therapy. Here, we found that coffee ingredients, namely caffeine and theobromine, decreased the protein level of CLDN2 in human lung adenocarcinoma-derived A549 cells. In contrast, other components, such as theophylline and chlorogenic acid, had no effect. These results indicate that the 7-methyl group in methylxanthines may play a key role in the reduction in CLDN2 expression. The caffeine-induced reduction in the CLDN2 protein was inhibited by chloroquine, a lysosome inhibitor. In a protein-stability assay using cycloheximide, CLDN2 protein levels decreased faster in caffeine-treated cells than in vehicle-treated cells. These results suggest that caffeine accelerates the lysosomal degradation of CLDN2. The accumulation and cytotoxicity of doxorubicin were dose-dependently increased, which was exaggerated by caffeine but not by theophylline in spheroids. Caffeine decreased nuclear factor-erythroid 2-related factor 2 (Nrf2) levels without affecting hypoxia-inducible factor-1α levels. Furthermore, caffeine decreased the expression of Nrf2-targeted genes. The effects of caffeine on CLDN2 expression and anticancer-drug-induced toxicity were also observed in lung adenocarcinoma RERF-LC-MS cells. We suggest that caffeine enhances doxorubicin-induced toxicity in A549 spheroids mediated by the reduction in CLDN2 and Nrf2 expression.
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Registered trials
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